Preparing isotactic stereoblock poly (lactic acid)

ABSTRACT

A stereospecific poly(lactic acid) is isotactic poly(lactic acid) having a number average molecular weight ranging from 10,000 to 200,000 grams per mole, with, on average, an equal number of poly (R) and poly (S) blocks where each block contains an average of 5 to 50 monomer units. Product was prepared by polymerizing rac-lactide in the presence of racemic catalyst consisting of:  
                 
 
     and the corresponding S-enantiomer or in the presence of racemic catalyst consisting of:  
                 
 
     and the corresponding S-enantiomer, wherein R is C 1 -C 4  alkyl which is straight chain or branched.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. ProvisionalApplication No. 60/242,470, filed Oct. 24, 2000.

[0002] This invention is made at least in part with Government Supportunder National Science Foundation Career Award CHE-9875261. TheGovernment has certain rights in the invention.

TECHNICAL FIELD

[0003] This invention is directed at an isotactic stereoblockpoly(lactic acid) and to methods of making an isotactic stereoblockpoly(lactic acid).

BACKGROUND OF THE INVENTION

[0004] Poly(lactic acid)s, PLAs, are considered to have utility formedical, agricultural, and packaging application due to theirbiocompatibility and biodegradability. In view of this, it is desirableto provide new stereospecific forms of poly(lactic acid)s and newmethods of preparing known forms of poly(lactic acid)s.

[0005] A convenient synthetic route to PLAs is the ring-openingpolymerization of lactide, the cyclic diester of lactic acid. A range ofmetal alkoxide initiators have been reported to polymerize lactide withretention of configuration. For example, these initiators have beenreported to polymerize optically active (R,R)-lactide or (S,S)-lactideto produce isotactic poly(lactic acid). Moreover, these initiators havebeen reported to polymerize rac-lactide to produce amorphous, atacticpolymers.

[0006] Heterotactic poly(lactic acid) is a stereospecific polymer thathas alternating pairs of stereogenic centers in the main chain. Thispoly(lactic acid) and the method of making it are disclosed in U.S.patent application Ser. No. 09/707,980, filed Nov. 8, 2000.

[0007] Spassky, N., et al., Macromol. Chem. Phys. 197, 2627-2637 (1996)reported the kinetic resolution of racemic lactide (rac-lactide) withthe methoxide variant of the R-enantiomer of catalyst used in theinvention herein. The high melting material that formed is considered tohave a tapered stereoblock microstructure, i.e., there was not a sharpdistinction between blocks and there were effectively two blocks.

SUMMARY OF THE INVENTION

[0008] It has been discovered herein that by polymerizing rac-lactide inthe presence of a racemic version of the catalyst used by Spassky, etal., that isotactic stereoblock poly(lactic acid) having several totalblocks where each block contains several monomer units, is formed.

[0009] One embodiment herein, denoted the first embodiment, is directedto isotactic stereoblock poly(lactic acid) having a number averagemolecular weight ranging from 10,000 to 200,000 grams per mole, with, onaverage, an equal number of poly (R) and poly (S) blocks where eachblock contains an average of 5 to 50 monomer units.

[0010] Another embodiment herein, denoted the second embodiment herein,is directed to preparing isotactic stereoblock poly(lactic acid) of thefirst embodiment herein comprising polymerizing rac-lactide in thepresence of a racemic catalyst consisting of:

[0011] and the corresponding S-enantiomer, where R is C₁-C₄ alkyl whichis straight chain or branched.

[0012] Still another embodiment herein, denoted the third embodimentherein, is directed to preparing isotactic stereoblock poly(lactic acid)of the first embodiment herein comprising polymerizing rac-lactide inthe presence of a racemic catalyst consisting of:

[0013] and the corresponding S-enantiomer, where R is C₁-C₄ alkyl whichis straight chain or branched.

[0014] The number average molecular weights (M_(n)) herein aredetermined by gel permeation chromatography (GPO).

DETAILED DESCRIPTION

[0015] We turn now to the embodiment directed to isotactic stereoblockpoly(lactic acid) having a number average molecular weight ranging from10,000 to 200,000 grams per mole, with, on average, an equal number ofpoly (R) and poly (S) blocks where each block contains an average of 5to 50 monomer units.

[0016] The stereoblock poly(lactic acid) prepared in Example I hereinhas a number average molecular weight of 22,600 grams per mole, with, onaverage, an equal number of poly (R) and poly (S) blocks where eachblock contains an average of 11 monomer units. The stereoblock(poly(lactic acid) prepared in Example II herein has a number averagemolecular weight of 29,560 grams per mole, with, on average, an equalnumber of poly (R) and poly (S) blocks where each block contains anaverage of 10 monomer units.

[0017] A structural formula for the isotactic stereoblock poly(lacticacid) of the first embodiment is:

[0018] where n averages from 5 to 50 and m averages from 2 to 200. Inthe formula I, n is the average number of monomer units in a block, andm is the number of blocks.

[0019] We turn now to the second embodiment herein, that is theembodiment directed to preparing isotactic stereoblock poly(lactic) acidcomprising polymerizing rac-lactide in the presence of a racemiccatalyst consisting of:

[0020] and the corresponding S-enantiomer, where R is C₁-C₄ alkyl whichis straight chain or branched. In the catalyst, the R- and S-enantiomersare in a 1:1 ratio.

[0021] The rac-lactide, that is racemic lactide, is an admixture of(R,R)-lactide and (S,S)-lactide in a 1:1 ratio. It is commerciallyavailable. (R,R)-lactide has the formula:

[0022] The catalyst (II) is prepared, for example, by synthesizing theR-enantiomer and the S-enantiomer and forming or using an admixturethereof in a 1:1 ratio. The R-enantiomer and the S-enantiomer of theligand of the complex can be prepared according to the proceduredescribed in Bermardo, K. D., et al., New J. Chem. 19, 129-131 (1995).Complex (II) and the corresponding S-enantiomer can be formed by heatingsolution of enantiomeric ligand and the appropriate aluminum alkoxide intoluene.

[0023] Examples of the catalyst are admixtures of corresponding R and Senantiomers of complex and include admixtures of complexes with theformula (II) where R is methyl or where R is isopropyl and thecorresponding S-enantiomers.

[0024] For the polymerization, the mole ratio of monomer to aluminum canrange, for example, from 10:1 to 1,000:1.

[0025] The polymerization is carried out, e.g., in an aprotic solvent,e.g., toluene or benzene, at a temperature ranging 50° C. to 100° C.,e.g., 70° C.

[0026] The stereoblock poly(lactic acid) of the Example I is prepared bythe method of the second embodiment.

[0027] Other stereoblock poly(lactic acid)s herein are prepared usingother racemic aluminum alkoxide catalysts in place of catalyst (II).

[0028] We turn now to the third embodiment herein, that is theembodiment directed to preparing isotactic stereoblock poly(lactic) acidcomprising polymerizing rac-lactide in the presence of a racemiccatalyst consisting of:

[0029] and the corresponding S-enantiomer, where R is C₁-C₄ alkyl whichis straight chain or branched. In the catalyst, the R- and S-enantiomersare in a 1:1 ratio.

[0030] The method of the third embodiment is the same as the method ofthe second embodiment except for the catalyst.

[0031] The catalyst for the third embodiment can be prepared as follows.The ligand used to prepare the catalyst can be prepared according to theprocedure described in Kanoh, S., et al., Polymer Journal 19, 1047-1065(1987). The racemic catalyst is prepared, for example, by heating asolution of racemic ligand and the appropriate aluminum alkoxide intoluene.

[0032] Elements of the invention are described in a publication ofOvitt, J. M., et al., titled “Stereoselective Ring-OpeningPolymerization of rac-Lactide with a Single-Site, Racemic AluminumAlkoxide Catalyst: Synthesis of Stereoblock Poly(lactic acid),” Journalof Polymer Science: Part A: Polymer Chemistry, Vol. 38, 4686-4692(2000), which is incorporated herein by reference.

[0033] The invention is illustrated by the following working examples:

EXAMPLE I

[0034] The catalyst used is the racemic catalyst consisting of (II) andthe corresponding S-enantiomer wherein R is isopropyl.

[0035] The R-enantiomer of the catalyst is synthesized as follows:

[0036] The starting material, i.e., the ligand is (R)-SalBinapH₂ whichhas the formula:

[0037] (R)-SalBinapH₂ can be obtained by the following reaction:

[0038] The ligand is converted into the R-enantiomer as follows: In aglove box, a dry Schlenk tube was loaded with freshly distilled aluminumisopropoxide (0.137 g, 0.671 mmol), (R)-SalBinapH₂ (0.329 g, 0.668mmol), and toluene (10 mL). The mixture was heated to 70° C. and stirredfor two days. The solvent was removed in vacuo, yielding a yellow solid.

[0039] The S-enantiomer was prepared by the same method as theR-enantiomer except that the ligand was (S)-SalBinapH₂.

[0040] The R-enantiomer was denoted (R)-1.

[0041] The S-enantiomer was denoted (S)-1.

[0042] The stereoblock polymer of the formula (I) was prepared asfollows: In the drybox, a dry Schlenk tube was loaded with (R)-1 as a0.0106 M solution in toluene (0.657 mL, 0.0069 mmol), (S)-1 as a 0.0117M solution in toluene (0.592 mL, 0.0069 mmol), rac-lactide (0.199 g,1.38 mmol), and toluene (6 mL). The flask was heated to 70° C. andstirred for 40 h. The reaction was quenched via rapid cooling withliquid N₂. The solvent was removed in vacuo, and the polymer wasdissolved in CH₂Cl₂ and precipitated from cold MeOH. A white crystallinesolid was isolated and dried in vacuo to a constant weight, with anisolated yield of 0.1985 grams.

[0043] The polymer obtained was isotactic poly(lactic acid) of the firstembodiment herein having a M_(n) of 22,600 grams per mole with anaverage of 11 lactide monomer units in each block. The melting point ofthe polymer was 179° C., which is higher than that of enantiomericallypure polymer, consistent with the cocrystallization of the enantiomericblocks of the polymer.

EXAMPLE II

[0044] The catalyst used is the racemic catalyst consisting of (III) andthe corresponding S-enantiomer.

[0045] Racemic ligand for preparing the catalyst, denotedrac-SalBiphenH₂ was prepared as follows: A 100 mL rb flask was loadedwith 2,2′-diamino-6,6′-dimethylbiphenyl (AMB) (0.222 g, 1/04 mmol),salicyaldehyde (0.223 mL, 2.09 mmol), and absolute EtOH (12 mL). Thereaction was heated to reflux with stirring under N₂ overnight. Thereaction was allowed to cool to RT and the yellow solid was filtered,concentrated, and dried in vacuo to constant weight. Yield=0.339 g. ¹HNMR (CDCl₃, 300 MHz: δ 12.30 (2H, s), 8.51 (2H, s), 7.39 (2H, t), 7.27(2H, d, J=7.3), 7.21-7.24 (4H, m), 7.15 (2H, d, J=8.1), 6.79-6.84 (4H,m), 2.05 (6H, s).

[0046] The catalyst was prepared from the racemic ligand according tothe general procedure used for catalyst preparation in Example I. In aglove box, a dry Schlenk tube was loaded with freshly distilled aluminumisopropoxide, rac-SalBiphenH₂ and toluene. The mixture was heated to 70°C. and stirred for two days. The solvent was removed, in vacuo, yieldinga yellow solid. The catalyst was denoted rac-(SalBiphen)AlO^(i)Pr.

[0047] Stereoblock polymer of the formula (I) was prepared as follows.In the drybox, a dry Schenk tube was loaded with a solution ofrac-(SalBiphen)AlO^(i)Pr in toluene, and rac-lactide (LA) with toluenebeing 0.2 M and [LA]/[Al] being 100. The flask was heated to 70° C. andstirred for 72 hours. The solvent was removed in vacuo, and the polymerwas dissolved in CH₂Cl₂ and precipitated from cold MeOH. A conversion of93% was achieved. The polymer exhibited a stereoblock microstructure.GPC revealed a M_(n)=29,560 grams per mole and a molecular weightdistribution M_(w)/M_(n)=1.06. The polymer was semicrystalline andexhibited a peak T_(m)=178° C. and a T_(g)=28.2° C. The polymercontained an average of 10 lactide monomer units in each block.

[0048] Variations

[0049] Many variations of the above will be obvious to those skilled inthe art. Thus the scope of the invention is defined by the claims.

What is claimed is:
 1. Isotactic stereoblock poly(lactic acid) having anumber average molecular weight ranging from 10,000 to 200,000 grams permole with, on average, an equal number of poly (R) and poly (S) blockswhere each block contains an average of 5 to 50 monomer units.
 2. Theisotactic stereoblock poly(lactic acid) of claim 1 having a M_(n) of22,600 grams per mole, with an average of 11 monomer units in eachblock.
 3. The isotactic stereoblock poly(lactic acid) of claim 1 havinga M_(n) of 29,560 grams per mole, with an average of 10 monomer units ineach block.
 4. A method for preparing the isotactic stereoblockpoly(lactic acid) of claim 2 which comprises polymerizing rac-lactide inthe presence of a racemic catalyst consisting of:

and the corresponding S-enantiomer, where R is C₁-C₄ alkyl which isstraight chain or branched.
 5. The method of claim 4 where R in thecatalyst is isopropyl and the polymerization is carried out at atemperature ranging fiom 50 to 100° C.
 6. A method of preparingisotactic stereoblock poly(lactic) acid of claim 3 which comprisespolymerizing rac-lactide in the presence of racemic catalyst consistingof:

and the corresponding S-enantiomer, where R is C₁-C₄ alkyl which isstraight chain or branched.
 7. The method of claim 6 where R in thecatalyst is isopropyl and the polymerization is carried out at atemperature ranging from 50 to 100° C.